Subject(s)
Hyperlipoproteinemia Type II/complications , Hyperlipoproteinemia Type II/genetics , Hypoalphalipoproteinemias/complications , Hypoalphalipoproteinemias/genetics , Adult , Apolipoprotein A-I/genetics , Apolipoproteins B/genetics , Apolipoproteins E/genetics , DNA Mutational Analysis , Family , Glucosylceramidase/genetics , Humans , Lipoprotein Lipase/genetics , Male , Morocco , Pedigree , Phosphatidylcholine-Sterol O-Acyltransferase/genetics , Polymorphism, Single Nucleotide , Receptors, LDL/geneticsABSTRACT
Familial hypercholesterolaemia (FH) is an autosomal dominant disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C) as a result of mutations that impair their removal from plasma.The clinical consequence is a high risk of premature cardiovascular disease. Because of the extreme risk of mortality and morbidity, diagnosis, recruitment and management of FH patients must be one of the priorities of public health. In Morocco, specialized consultation for dyslipidaemia and strategy for management of this cardiovascular major risk factor does not exist, making FH identification and management difficult. In this review, we present the first FH state of the art in our country through a sample of 66 subjects. By this analysis, we have tried to elucidate some points that impede the identification and recruitment of heterozygous FH and the management of both heterozygous and homozygous FH in Morocco. Also, we have attempted to propose some strategies for an adequate management of FH in our country, taking into account the local specifications.
Subject(s)
Hyperlipoproteinemia Type II/drug therapy , Apolipoproteins B/genetics , Cholesterol, LDL/blood , Cholesterol, LDL/drug effects , Coronary Artery Disease/blood , Coronary Artery Disease/etiology , Coronary Artery Disease/genetics , Coronary Artery Disease/prevention & control , Genetic Predisposition to Disease , Genotype , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/complications , Hyperlipoproteinemia Type II/genetics , Hypolipidemic Agents/therapeutic use , Morocco , Mutation , Proprotein Convertase 9 , Proprotein Convertases , Receptors, LDL/genetics , Serine Endopeptidases/geneticsABSTRACT
Familial hypercholesterolemia (FH) is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor (LDLR) gene, although it can also be due to alterations in the gene encoding apolipoprotein B (familial defective apoB or FDB) or in other unidentified genes. In Morocco, the molecular basis of FH is unknown. To obtain information on this issue, 27 patients with FH from eight unrelated families were analyzed by screening the LDLR (PCR-SSCP and Southern blot) and apoB genes (PCR and restriction enzyme digestion analysis). None of the patients carried either the R3500Q or the R3531C mutation in the apoB gene. By contrast, seven mutations in the LDLR gene were identified, including five missense mutations on exons 4, 6, 8, and 14 (C113R, G266C, A370T, P664L, C690S) and two large deletions (FH Morocco-1 and FH Morocco-2). The two major rearrangements and the missense mutation G266C are novel mutations and could well be causative of FH in the Moroccan population. This study has yielded preliminary information on the mutation spectrum of the LDLR gene among patients with FH in Morocco.
